纳米二氧化钛致小鼠肝组织DNA氧化损伤的研究

[目的]探讨纳米二氧化钛对小鼠DNA的氧化损伤作用. [方法]将20只雌性小鼠随机分成对照组和低、中、高3个染毒组,每组5只动物,采用尾静脉注射染毒;各组纳米二氧化钛染毒剂量分别为0、100、200、400mg/kg体重;动物染毒后24h处死,碘化钠法提取小鼠肝、肺、肾、骨髓、大脑组织中的DNA,采用高效液相色谱-ECD(HPLC-ECD)法测定各组织中的8-羟基脱氧鸟苷(8-OHdG),观察纳米二氧化钛对不同组织DNA的氧化损伤情况. [结果]低、中、高3个染毒组的肝脏DNA水平分别是每106个脱氧鸟苷(dG)中含8-OHdG个数(1.07±0.11)、(1.49±0.13)、(1.39±0.18),高于对照组(0.82±0.06),差异有统计学意义(P＜0.01);各染毒组其他脏器组织中8-OHdG水平与对照组比较,差异无统计学意义(P＞ 0.05). [结论]纳米二氧化钛可导致小鼠肝脏DNA氧化损伤增加,对肺、肾、骨髓、大脑中的DNA氧化损伤未见影响.     

大剂量甲泼尼龙可能加速急性百草枯中毒小鼠死亡的初步研究

目的观察大剂量甲泼尼龙琥珀酸钠对于急性百草枯(paraquat,PQ)中毒小鼠的疗效。方法 65只Balb/c小鼠随机分成染毒组30只、治疗组30只和甲泼尼龙对照组5只;P染毒组依据染毒不同剂量PQ(50、70、100、150、200、300 mg/kg)随机分成6组,治疗组在小鼠染毒不同剂量的PQ后均加用大剂量甲泼尼龙琥珀酸钠(195 mg/kg),甲泼尼龙对照组仅给予甲泼尼龙琥珀酸钠(195 mg/kg);比较染毒组和治疗组的半数致死量。结果(1)染毒组小鼠在染毒后24 h、48 h、72 h的LD50分别为216.67 mg/kg、216.67 mg/kg和188.24 mg/kg;治疗组小鼠在染毒后24 h、48 h、72 h的LD50分别为70.42 mg/kg、70.42 mg/kg和87.66 mg/kg。(2)治疗组小鼠染毒后24 h、48 h、72 h的LD50明显小于染毒组。结论急性PQ中毒Balb/c小鼠腹腔注射大剂量甲泼尼龙琥珀酸钠后可能加速其死亡。 更多还原     

一次性腹腔内铅染毒对小鼠卵巢颗粒细胞凋亡率的影响

为探讨铅对小鼠卵巢颗粒细胞凋亡率的影响,本研究将72只25日龄SPF级ICR雌性小鼠随机分为1和2mg/kg乙酸铅染毒组和对照组(生理盐水),每组24只.预饲2 d后,每只小鼠腹腔注射8 IU囊泡包埋的促卵泡素(FSH).48 h后,腹腔注射染毒乙酸铅,染毒剂量为0.2 ml/只.分别于染毒后48和96 h用流式细胞仪测定卵巢颗粒细胞凋亡率.结果 显示.染毒48 h后,对照组和1、2mg/kg乙酸铅染毒组颗粒细胞凋亡率分别为(7.6666±1.9675)%,(6.1000±0.435 9)%,(6.833 3±1.238 7)%,3者间比较,差异无统计学意义(P＞0.05).染毒96 h后,1、2 mg/kg乙酸铅染毒组颗粒细胞凋亡率分别为(16.9000±2.433 8)%和(22.933 3±4.543 3)%.均高于对照组[(8.2000±1.50444)%1,差异有统计学意义(P＜0.05).与染毒48 h比较.染毒96 h后各乙酸铅染毒组的细胞凋亡率均较高,差异有统计学意义(P＜0.05).表明铅对卵巢颗粒细胞凋亡的促进作用具有时间依赖性和一定的剂量相关性.     

全氟辛烷磺酸对小鼠脾细胞NO分泌水平影响

目的观察短期、高剂量全氟辛烷磺酸(PFOS)对C57BL/6雄性小鼠一氧化氮(NO)分泌水平影响。方法选择雄性C57BL/6小鼠24只,PFOS经口灌胃染毒,剂量分别为5,20,40 mg/kg。每天1次,染毒7 d后,制备脾脏淋巴细胞悬液,细胞培养48 h后收取上清液,检测NO含量。结果20,40 mg/kg PFOS染毒组小鼠体重明显下降(P0.05);20 mg/kg PFOS染毒组小鼠脾脏和胸腺指数分别为(0.36±0.04)和(0.21±0.02),明显低于对照组(P0.05)。40 mg/kg PFOS染毒组NO分泌水平为(0.66±0.14)μmol/L,明显低于对照组(P0.05)。结论高剂量PFOS暴露可降低小鼠脾淋巴细胞NO分泌水平,抑制小鼠巨噬细胞的活化。     

敌敌畏、乐果和马拉硫磷混合染毒对雄性小鼠生殖功能的影响

目的 研究敌敌畏、乐果和马拉硫磷混合染毒后对雄性小鼠生殖功能影响的特点和可能机制。方法 将105只雄性ICR小鼠按体重分层随机分成7组,每组15只,即对照组(0 mg/kg),敌敌畏、乐果和马拉硫磷混合低( 10.8 mg/kg)、中(21.5mg/kg)、高剂量组(43.0 mg/kg),以及敌敌畏组(5.1 mg/kg)、乐果组(12.6 mg/kg)和马拉硫磷组(25.3 mg/kg),经口连续灌胃染毒35 d,每天1次。染毒第36天后处死动物。测量小鼠体重、精子活力,观察精子数量及精子畸形率,检测血清中性激素[包括睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)等]的水平,并观察睾丸及附睾的病理及电镜下改变。结果 染毒后第14天,混合高剂量组小鼠体重[(22.40±3.07)g]低于对照组[(26.73±2.82)g](P＜0.05);染毒后第28天,混合中剂量组小鼠体重[(30.00±4.93)g]亦低于对照组[(33.13±3.29)g](P ＜0.05)。混合中、高剂量组精子数[分别为(321.17±18.19)×106/g附睾重、(225.00±19.67)×106/g附睾重]和精子活力[分别为(64.67±9.91)％、(57.83±9.66)％]均低于对照组[分别为( 373.33±14.65)× 106/g附睾重、(75.17±7.68)％](P值均＜0.05);精子畸形率[分别为(43.33 ±8.66)‰、(55.00±13.80)‰]高于对照组[(32.67±8.17)‰]（P值均＜0.05）;与对照组相比[FSH、E2、LH、T分别为(1.41±0.20)、(17.32±2.72)、(8.75±1.32)、（3.45±0.80）nmol/L],混合中、高剂量组小鼠血清中FSH[分别为(3.14±0.62)、(3.85±0.37) nmol/L]、E2[分别为(36.81±6.68)、（43.76±9.82）nmol/L]水平升高（P值均＜0.01）,LH[分别为(5.21 ±1.23)、(4.27±1.09) nmol/L]、T[分别为(1.37±0.38)、(0.73±0.18)nmol/L]水平降低（P值均＜0.01）。混合高剂量组小鼠睾丸成熟精子数减少,并可见结构异常的精子头、精子尾。结论 敌敌畏、乐果和马拉硫磷混合联合染毒可直接损害小鼠睾丸及附睾的结构和功能,而导致生殖细胞生成过程异常;并导致下丘脑-垂体-性腺轴性激素的分泌紊乱。     

镉亚急性暴露对小鼠肝肾功能及甲基化水平的影响

[目的]初步探讨氯化镉(cadmium chloride,CdCl2)亚急性暴露(4周染毒)对小鼠肝肾功能、全基因组甲基化水平及去甲基化酶Tet1表达的影响. [方法]将48只SPF级KM小鼠(昆明小鼠,雌雄各半)随机分为4组:对照组(ddH2O)、CdCl2 17.5 mg/kg组、25 mg/kg组、35 mg/kg组.经口灌胃染毒(每天1次、每周5d),共染毒4周,CO2麻醉法处死动物.测定肝脏和肾脏的脏器系数、血液常规及血液生化检查、肝肾组织病理学检查、全基因组DNA甲基化水平及Tet1酶表达水平. [结果]35 mg/kg染毒组小鼠活动度及精神状态较差.小鼠体重在各染毒周期和染毒剂量组间差异均有统计学意义,且存在交互作用(P＜ 0.05).与对照组相比,雄性小鼠肝脏质量和肝脏脏器系数在25 mg/kg和35 mg/kg剂量组差异具有统计学意义(P＜0.05);血液常规检查结果显示,雌、雄性小鼠35 mg/kg染毒组血液白细胞(WBC)、血小板(PLT)、淋巴细胞(LYM)计数,均高于对照组(P＜0.05);雄性小鼠在各个染毒剂量组间,WBC、PLT、LYM、RBC计数差异有统计学意义(P＜0.05).此外,血生化实验结果显示,各剂量组雄性和雌性小鼠中肝功能的主要指标谷丙转氨酶(ALT)、碱性磷酸酶(ALP)差异有统计学意义(P＜0.05),肾功能的主要指标尿酸(UA)、血尿素氮(BUN)、肌酐(CR)差异均有统计学意义(P＜0.05).组织病理学分析发现25 mg/kg和35 mg/kg组雄性小鼠肝脏及肾脏呈现明显的病理性改变.Tet1 mRNA及其蛋白表达水平仅在雄性小鼠的肝脏、肾脏中表达的差异有统计学意义(P＜0.05).焦磷酸测序结果显示,雄性小鼠肝脏、肾脏甲基化水平表达差异有统计学意义(P＜0.05),且其与Tet1 mRNA表达呈负相关(r=-0.473,P＜0.05;r=-0.134,P＜0.05). [结论]CdCl2亚急性染毒可以诱导小鼠肝肾功能损伤,且对全基因组甲基化水平和去甲基化酶Tet1表达呈现出性别差异影响,雄性小鼠的肝肾组织Tet1表达参与调控全基因组DNA甲基化水平改变.     

纳米二氧化钛对小鼠卵巢组织中甾醇O-酰基转移酶1与类固醇合成急性调节蛋白表达的影响

目的研究纳米二氧化钛染毒对小鼠卵巢组织中甾醇O-酰基转移酶1(SOAT1)与类固醇合成急性调节蛋白(STAR)表达的影响。方法将48只40日龄清洁级ICR雌性小鼠随机分为4组,分别为对照(0.5%羧甲基纤维素)组和25、50、100 mg/kg纳米二氧化钛染毒组,每组12只。通过灌胃方式进行染毒,染毒容积为10 ml/kg,每天1次,连续染毒60 d。采用基因芯片检测100 mg/kg纳米二氧化钛染毒60 d小鼠卵巢组织中类固醇代谢相关基因表达的影响。采用实时定量PCR法检测100 mg/kg纳米二氧化钛染毒60 d后卵巢组织SOAT1与STAR基因表达的水平。使用ELISA法检测各剂量纳米二氧化钛染毒15、30、60 d后卵巢组织SOAT1与STAR蛋白水平。结果与对照组比较,以差异值≥13分或≤-13分为筛选标准,在100 mg/kg纳米二氧化钛染毒60 d小鼠卵巢中已知功能为类固醇代谢的差异表达基因中,Soat1、Star、Cyp17a1和Cyp11a1表达上调,Cyp2b1、Akr1c19和Cyp2a5表达下调。与对照组比较,100 mg/kg纳米二氧化钛染毒60 d小鼠卵巢中SOAT1与STAR基因实时定量PCR法的检测结果上调(P0.01),与芯片结果一致。与对照组比较,50 mg/kg纳米二氧化钛染毒60 d和100 mg/kg纳米二氧化钛染毒30、60 d小鼠卵巢组织中STAR与STAR的蛋白水平上升,差异均有统计意义(P0.05);且随着纳米二氧化钛染毒剂量的升高和染毒时间的延长,小鼠卵巢组织中SOAT1与STAR的水平呈现上升趋势。结论纳米二氧化钛暴露通过促进小鼠卵巢组织中SOAT1与STAR的表达,干扰卵巢类固醇代谢。     

纳米与微米级二氧化硅粉尘对小鼠氧化和抗氧化指标的影响

目的 观察纳米SiO2和微米SiO2粉尘对雄性小鼠血清中超氧化物歧化酶(SOD)同工酶活力、丙二醛(MDA)含量、总抗氧化能力(TAOC)的影响.方法 将70只昆明种小鼠随机分成7组,每组lO只,设1个对照组,6个染毒组(纳米SiO2组50、100、200mg/m3,微米SiO2组50、100、200mg/m3),染尘14 d,每天1 h,染尘结束后测定小鼠血清中SOD活力、MDA含量、TAOC水平.结果 与对照组比,纳米SiO2 50 mg/m3组SOD活力[(217.46±118.07)U/ml]明显降低,100、200 mg/m3组SOD活力明显增高,差异有统计学意义(P＜0.05);纳米SiO2 100、200 mg/m3 组MDA含量明显低于对照组,差异有统计学意义(P＜0.05).随剂SiO2染尘量增加,微米SiO2组SOD活力呈降低趋势,MDA含量呈现增高趋势,与对照组比较,差异有统计学意义(P＜0.05).各纳米SiO2组TAOC分别为(8.24±1.15)、(12.60±3.53)、(9.52±3.53)U/ml,与相应微米组SiO2相比,TAOC明显降低,差异有统计学意义(P＜0.05).结论 纳米与微米SiO2粉尘均对小鼠产生氧化损伤作用,纳米SiO2粉尘对小鼠的氧化损伤作用更严重.     

纳米TiO_2对雌性小鼠的生殖毒性

目的探讨纳米TiO_2对雌性小鼠的生殖毒性效应。方法将60只健康SPF级雌性ICR小鼠随机分为4组,分别为对照(生理盐水)组和10、50、100 mg/kg/d纳米TiO_2染毒组,每组15只,连续28天灌胃染毒。检测小鼠生殖脏器系数、阴道涂片观察动情周期、HE染色观察卵巢组织变化、试剂盒测定卵巢中超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化物酶(POD)及过氧化氢酶(CAT)水平。结果染毒后,与对照相比,50和100 mg/kg/d染毒组,小鼠动情前期明显缩短(P0.05),动情后期显著延长(P0.05);卵巢组织HE切片观察发现,纳米TiO_2染毒组中,小鼠卵巢颗粒细胞和黄体均出现不同程度的结构疏松和炎症细胞浸润;氧化应激测定结果表明,50和100 mg/kg/d染毒组小鼠卵巢SOD活性显著低于对照组(P0.05);与对照相比,各染毒组MDA含量均显著增加(P0.05);POD和CAT活性分别在100和50、100 mg/kg/d剂量组明显高于对照组(P0.05)。结论纳米TiO_2可引起小鼠动情周期紊乱及卵巢组织的氧化损伤。     

Joint Toxic Effect of Formaldehyde and Xylene on Nervous System of Mice

目的 研究甲醛和二甲苯联合染毒对小鼠神经系统的毒性作用及其机制,为综合评价室内装修材料中甲醛和二甲苯对人体健康的危害提供科学依据.方法 选用健康清洁级昆明小鼠72只,按完全随机设计,将小鼠随机分为12组,每组6只,雌雄各半,分别为低剂量(5mg/kg)、中剂量(10mg/kg)、高剂量甲醛染毒组(20mg/kg)和生理盐水对照组,低剂量(50mg/kg)、中剂量(100mg/kg)、高剂量二甲苯染毒组(150mg/kg)和花生油对照组以及低剂量(2.5mg/kg甲醛+25mg/kg二甲苯)、中剂量(5mg/kg甲醛+50mg/kg二甲苯)、高剂量联合染毒组(10mg/kg甲醛+75mg/kg二甲苯)以及生理盐水+花生油(体积比1:1)对照组;采用腹腔注射染毒,连续7d.染毒结束后,采用Morris水迷宫实验和流式细胞凋亡对小鼠进行神经毒性的研究.结果 与相应对照组相比,中、高剂量甲醛、二甲苯以及联合染毒组小鼠逃避潜伏期延长,差异均有统计学意义(P＜0.05);与相同剂量联合染毒组比较,中、高剂量甲醛、二甲苯联合染毒组雌性小鼠逃避潜伏期缩短,差异均有统计学意义(P＜0.05);随着染毒时间的延长,各染毒组小鼠总体逃避潜伏期呈缩短趋势.在空间探索实验中,与相应对照组相比,中、高剂量甲醛、二甲苯染毒组以及各剂量联合染毒组小鼠找到平台的时间延长,在原平台象限游泳时间缩短,原平台象限游泳距离占总距离百分比下降,差异均有统计学意义(P＜0.05);与相同剂量联合染毒组比较,各剂量甲醛染毒组和中、高剂量二甲苯染毒组小鼠找到平台的时间缩短,高剂量甲醛染毒组和二甲苯染毒组雌性小鼠、雄性小鼠以及小鼠总体在原平台象限游泳时间延长,原平台象限游泳距离占总距离百分比上升,差异有统计学意义(P＜0.05).与相应对照组相比,各剂量甲醛、二甲苯以及联合染毒组小鼠海马细胞早期凋亡率以及高剂量甲醛、二甲苯以及联合染毒组晚期凋亡率均升高,差异均有统计学意义(P＜0.05);且随着染毒剂量的升高,小鼠海马细胞早期、晚期凋亡率呈上升趋势.与相同剂量联合染毒组比较,中、高剂量甲醛、二甲苯染毒组小鼠早期凋亡率均下降,高剂量甲醛、二甲苯染毒组雌性小鼠、雄性小鼠和小鼠总体晚期凋亡率均下降,差异均有统计学意义(P＜0.05).结论 甲醛和二甲苯联合染毒能降低小鼠的学习记忆能力,对神经系统具有一定毒性作用,且二者联合染毒具有一定的协同作用.     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.